The Role of Neurogenesis and APP in Alzheimer’s Disease

by Amir Hussein
5 comments
neurogenesis timing

New Insights into Human Neurogenesis and Alzheimer’s Disease

A recent study conducted by researchers at the Paris Brain Institute has shed light on the process of neurogenesis, which involves the formation of neural cells from stem cells in humans. This groundbreaking research suggests that the timing of neurogenesis may be linked to the development of neurodegenerative diseases like Alzheimer’s. Specifically, the study indicates that abnormalities in the expression of the amyloid precursor protein (APP) could result in a normally functioning brain at birth but increased susceptibility to neurodegeneration later in life.

Amyloid Precursor Protein’s Influence on Human Brain Development

The research conducted at the Paris Brain Institute has revealed a significant role played by the amyloid precursor protein (APP) in regulating the development of the human brain. APP, commonly associated with Alzheimer’s disease, has been found to influence the timing of neurogenesis. The absence of APP leads to accelerated production of neurons, suggesting a potential connection between the timing of neurogenesis and the onset of neurodegenerative diseases. These findings suggest that early vulnerabilities during neurogenesis may contribute to neurodegeneration later in life.

Understanding Neurogenesis in Humans

Neurogenesis, the process of neural cell formation from stem cells, begins in the fetus around 5 weeks gestation and is nearly complete by 28 weeks in the cerebral cortex. This intricate process involves finely tuned mechanisms.

According to Khadijeh Shabani, a post-doctoral researcher at the Paris Brain Institute, neurogenesis in humans lasts longer compared to other species. Neural stem cells remain in a progenitor state for an extended period before differentiating into glial cells, astrocytes, or oligodendrocytes, which form the brain and spinal cord’s architecture.

Unveiling the Role of APP in Neuronal Production

The researchers focused on investigating the amyloid precursor protein (APP), which is expressed throughout the nervous system’s development. Bassem Hassan, the leader of the “Brain Development” team at the Paris Brain Institute, states that APP is an intriguing research target due to its fragmentation, which produces amyloid peptides. These peptides are associated with the toxic aggregation observed in Alzheimer’s disease and suggest that APP may play a central role in the disease’s early stages.

APP is known to be involved in various biological processes in many species, such as cerebral lesion repair, cellular response orchestration after oxygen deprivation, and brain plasticity regulation. In the case of human neurogenesis, APP’s expression is particularly significant during the differentiation and migration of cortical neurons. The researchers used cell sequencing data and the CRISPR-Cas9 technique to study APP’s role in human brain development. They found that APP regulates the timing of neurogenesis by influencing two finely tuned genetic mechanisms: stem cell proliferation control and the activation of new neuron production.

Unique Characteristics of Human Neurogenesis

Unlike in rodents, the loss of APP significantly accelerates brain neurogenesis in humans. This discrepancy suggests that APP’s regulatory role is negligible in mice but essential for the neurodevelopment of humans. The human brain requires the generation of a large number of neurons over an extended period to achieve its final form. Any abnormalities related to APP could lead to premature neurogenesis and significant cellular stress. These consequences may manifest later in life, particularly in the brain regions where early signs of Alzheimer’s disease are observed, which also undergo the longest maturation during childhood and adolescence.

The Link Between Neurogenesis Timing and Neurodegeneration

Is there a direct link between the timing of neurogenesis and the mechanisms underlying neurodegeneration? While neurodegenerative diseases are typically diagnosed between the ages of 40 and 60, clinical signs often appear decades after the initial decline in certain neuronal connections. This loss of connectivity may indicate molecular anomalies present since childhood or even earlier.

Further research is necessary to confirm whether APP plays a central role in the neurodevelopmental disruptions that contribute to the onset of Alzheimer’s disease. If so, it could be considered that these disruptions lead to the formation of a brain that initially functions normally but becomes particularly vulnerable to biological events (such as inflammation, excitotoxicity, or somatic mutations) and environmental factors (such as poor diet, lack of sleep, or infections). Over time, these stresses may contribute to neurodegeneration, a phenomenon specific to the human species that becomes more apparent with increasing life expectancy.

Reference: “The temporal balance between self-renewal and differentiation of human neural stem cells requires the amyloid precursor protein” by Khadijeh Shabani, Julien Pigeon, Marwan Benaissa Touil Zariouh, Tengyuan Liu, Azadeh Saffarian, Jun Komatsu, Elise Liu, Natasha Danda, Mathilde Becmeur-Lefebvre, Ridha Limame, Delphine Bohl, Carlos Parras, and Bassem A. Hassan, 16 June 2023, Science Advances.
DOI: 10.1126/sciadv.add5002

Frequently Asked Questions (FAQs) about neurogenesis timing

What is neurogenesis and how does it relate to Alzheimer’s disease?

Neurogenesis is the process of forming new neural cells from stem cells. It has been discovered that the timing of neurogenesis in humans may be linked to the development of neurodegenerative diseases like Alzheimer’s. Abnormalities in the expression of the amyloid precursor protein (APP) during neurogenesis can potentially make the brain more susceptible to neurodegeneration later in life.

What role does the amyloid precursor protein (APP) play in human brain development?

The amyloid precursor protein (APP) has a significant role in regulating human brain development. It influences the timing of neurogenesis, the process by which neural cells are formed. Studies have shown that the absence of APP leads to accelerated neuron production. APP-related abnormalities could cause premature neurogenesis and potentially contribute to neurodegenerative diseases later in life.

How long does neurogenesis last in humans and why is it important?

Neurogenesis in humans begins in the fetus at around 5 weeks gestation and is almost complete by 28 weeks in the cerebral cortex. It lasts longer in humans compared to other species. This prolonged neurogenesis is crucial for the development of the brain, as it allows for the generation of a large number of neurons over an extended period. The timing of neurogenesis plays a critical role in shaping the architecture of the brain and spinal cord.

Is there a connection between neurogenesis timing and the onset of neurodegenerative diseases?

Research suggests that there may be a link between the timing of neurogenesis and the onset of neurodegenerative diseases such as Alzheimer’s. While these diseases are typically diagnosed later in life, clinical signs may appear decades after the initial decline in certain neuronal connections. Anomalies during neurogenesis could potentially contribute to vulnerabilities that manifest as neurodegeneration later in life.

What further research is needed to understand the role of APP in neurodevelopmental disruptions and Alzheimer’s disease?

Further studies are necessary to confirm the central role of the amyloid precursor protein (APP) in neurodevelopmental disruptions that pave the way for Alzheimer’s disease. Researchers need to explore whether APP-related disturbances lead to the formation of a brain that functions normally at birth but becomes vulnerable to certain biological events and environmental factors over time. Investigating these factors will contribute to a better understanding of the mechanisms underlying neurodegenerative diseases.

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5 comments

SciFiGeek42 June 23, 2023 - 8:16 pm

woah, so the timing of neurogenesis could be linked to when neurodegenerative diseases start showing symptoms? that means problems might start way before we even realize it. gotta take care of our brains from the beginning!

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Brainiac88 June 23, 2023 - 9:13 pm

neurogenesis is sooo impoRTant for brain development and now we know that amyloid precursor protein plays a big role. app seems to be like a conductor for neuronal production. crazy how things can go wrong and lead to neurodegeneration.

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JaneDoe18 June 24, 2023 - 2:08 am

wow this is so fascinating! never knew that neurogenesis had such a big impact on alzheimers. can u imagine vulnerabilities being present right from birth? mindblowing stuff!

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CuriousCat June 24, 2023 - 7:47 am

i always wondered how long neurogenesis lasted in humans. 5 weeks to 28 weeks, that’s quite a long time! and it’s interesting how different it is in mice. maybe that’s why they don’t get affected by app deprivation like we do. our brains are unique!

Reply
Dreamer123 June 24, 2023 - 7:51 am

the more we learn about neurogenesis and app, the more we understand the complexities of our brains. it’s like a delicate dance between stem cell proliferation and neuron production. can’t wait for more research on this!

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